Acute pancreatitis (AP) is increasingly recognized in children, with an incidence approaching that of adults. Most children with pancreatitis have a single, mild, acute episode that resolves without complications. However, a subset of children with AP develops recurrent episodes (defined as acute recurrent pancreatitis or ARP) and some progress to chronic pancreatitis (CP). Few studies have been performed to characterize ARP and CP in children. We recognized that the lack of a well-phenotyped pediatric cohort presented a major obstacle in understanding the pathophysiology of CP and its sequelae. To address this knowledge gap, we have formed INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In search for a cuRE), composed of 18 participating sites. Results from 301 pediatric patients enrolled into our study revealed a high frequency of pancreatitis-associated gene mutations and substantial disease burden in children with CP. The objective of this application is to determine the natural history of pediatric CP, identify risk factors and genetic modifiers for its onset and sequelae and develop approaches to improve clinical outcomes. The overall hypothesis of this proposal is that pediatric CP has unique characteristics that determine disease onset and sequelae. Our specific aims are: 1) Characterize pediatric CP, determine predictors of disease severity and progression from ARP to CP; 2) Define the role of genetic mutations in early onset CP and identify disease modifiers; 3) Determine the efficacy of early pain management using cognitive-behavioral intervention on pediatric CP. Our long-term goal is to develop diagnostic modalities, prognostic factors and innovative treatment approaches for pediatric ARP and CP.